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Biomedical subjects

M Papa

Publications and source records attributed to M Papa.

At least 37 records · Page 2Linked to original sources
PubMed1998

Reduced transduction mechanisms in the anterior accumbal interface of an animal model of Attention-Deficit Hyperactivity Disorder.

The aim of this study was to map the neural substrates of attention-deficit hyperactivity disorder (ADHD) in the spontaneously hypertensive rat (SHR), which is thought to be a model for ADHD. To this aim, the Ca2+/calmodulin-dependent protein kinase II (CaMKII) and transcription factors (TF) were used as markers. The focus of interest was the nucleus accumbens complex (ACB) which is thought to be an interface between limbic and motor systems. Juvenile, male rats of the SHR line and Wistar-Kyoto (WKY) controls were perfused and the brains processed for immunocytochemistry for CaMKII and the TF peptides of the FOS, JUN-B and ZIF-268 families. The results revealed that: (i) in both groups there were more CaMKII-positive neurones in the shell than in the core of the ACB; (ii) SHR had a reduced number of CaMKII-positive elements in anterior portions of the shell; and (iii) SHR had a lower expression of peptide products of the FOS family (c-FOS, in particular) and ZIF-268. In addition, there was a lower expression of c-FOS and zif-268 in the core of the ACB in the SHR. In contrast, there was an increased basal level of JUN-B in the core of the ACB of SHR. The reduced number of CaMKII and TF-positive elements in the most rostral portions of the accumbal complex of SHR, associated to the higher number of binding sites for the DA D-1/D-5 subtype, appears as a discrete alteration in the prosomeric development of the anterior basal forebrain and could be the key to the understanding of ADHD.

Animals↗
PubMed1998

A quantitative cytochrome oxidase mapping study, cross-regional and neurobehavioural correlations in the anterior forebrain of an animal model of Attention Deficit Hyperactivity Disorder.

The aim of this study was to trace by molecular imaging techniques the neural substrates of attention deficit hyperactivity disorder (ADHD) using the spontaneously hypertensive rat (SHR) as animal model. Adult SHR and Wistar-Kyoto (WKY) controls were used throughout this study. In experiment 1, naive male SHR and WKY were used, whereas in experiment 2 SHR and WKY rats of both genders were trained on a multiple fixed interval (FI (120 s for water, 5-min extinction)) paradigm and sacrificed 6 months later. In both experiments coronal sections of the anterior forebrain were processed for quantitative cytochrome oxidase (COase) histochemistry by the method of Gonzalez-Lima. Optical density values were transformed into actual enzyme activity units by using tissue-calibrated standards. In experiment 1, non-trained male rats of the SHR line showed lower COase activity in the medial and lateral prefrontal cortices, compared with WKY controls. In experiment 2, there was a line x treatment interaction effect in the pole of the nucleus accumbens (ACB). Regional correlative analyses revealed that: (i) under basal conditions, SHR are more synchronized than WKY rats in the COase level of different brain regions; and (ii) the training desynchronizes COase activity in the WKY, further synchronizes it and increases the cross-talk between hemispheres in male SHR only. Neurobehavioral covariations between behavioural scores and metabolic capacity in the medial and lateral prefrontal/frontal cortices, the caudate-putamen complex (CPU), the pole, core, and shell of the accumbal complex (ACB), and the ventral pallidum (VP), indicated that, in the WKY rats, the frequency of lever pressing covaried positively with the COase activity in the CPU, whereas in the SHR covaried with both medial and lateral prefrontal/frontal cortices. The bursts of activity during the 1-1.33-s segment was positively correlated, in the WKY rats only, with the core and shell of the ACB, and with the VP. Finally, the correlative profiles showed significant gender differences with effects in male SHR only. Thus, the results lend support to the involvement of the cortico-striato-pallidal system in ADHD.

Animals↗
PubMed1997

Differential expression of transcription factors in the accumbens of an animal model of ADHD.

Transcription factors have been used as neuronal markers in the nucleus accumbens (ACB) of male juvenile spontaneously hypertensive rats (SHR), an animal model of attention-deficit hyperactivity disorder (ADHD), to trace putative neural substrates. In SHR, immunocytochemistry and PC-assisted image analysis showed lower expression of pan-fos, c-fos, zif/268 in the shell, and the c-fos and zif/268 in the core, with an increased level of Jun-B in the core. The differential lower basal expression of transcription factors in the ACB of an animal model of ADHD implies a reduced number of modules and might represent a neural substrate of the attention deficits seen in SHR and children with ADHD at low motivational levels.

Animals↗
PubMed1997

Oral premedication with midazolam in paediatric anaesthesia. Effects on sedation and gastric contents.

The aim of this study was to assess oral premedication with midazolam in paediatric anaesthesia. Sedation, quality of induction, recovery time, acceptance and effects on gastric contents were analysed. This prospective, double blind, at random and controlled study was performed in 107 children, aged between three and ten years. They were divided into: group 1 (control, n = 29), group 2 (placebo) receiving 5 ml of water in the preoperative stage (n = 40), and group 3 (midazolam) with 0.75 mg.kg-1 midazolam by mouth (n = 38). Two children refused to take medication. In children aged five years or more (n = 48) of groups 2 and 3, acceptance of premedication was evaluated. The midazolam group showed a better level of sedation as compared with the placebo (P < 0.05). The recovery time was similar for the two groups. There were no statistically significant differences in gastric pH or residual volume among the three groups. It is concluded that midazolam given by mouth is an efficient and safe drug for premedication in paediatric anaesthesia.

Adjuvants, Anesthesia↗
PubMed1996

High frequency of BRCA1 185delAG mutation in ovarian cancer in Israel. National Israel Study of Ovarian Cancer.

OBJECTIVE: To determine the role of BRCA1 185delAG mutation in ovarian carcinogenesis. DESIGN: Genetic testing of a subset of cases from an ongoing study of ovarian cancer and of controls. SETTING: A community-based case-control incidence study. SUBJECTS: Seventy-nine patients with ovarian cancer, 62 hospitalized women without cancer (controls), and 120 healthy women participating in a fragile X screening program (also controls), examined for the presence of germline BRCA1 185delAG mutation. MAIN OUTCOME MEASURES: Polymerase chain reaction-amplified BRCA1 exon 2 fragments generated from patients' and controls' blood samples, analyzed by heteroduplex gel shift assay and direct sequence analyses. RESULTS: The 185delAG mutation was detected in 38.9% (7/18) of ovarian cancer patients with familial history, and 13.1% (8/61) of family history-negative ovarian cancer cases. Only 1 carrier was detected among the 120 healthy controls, and none in the hospital controls. A significant difference in mutation carrier rates between family history-negative cases and control groups of 120 and 62 subjects was identified (Fisher exact test, P=.001 and P=.003, respectively). The median age (+/-SE) at disease diagnosis was lower among both familial and family history-negative mutation carriers, as compared with mutation-negative, family history-negative cases--50 (+/-1.4) vs 60.5 (+/-3.5) years old, respectively (hazard ratio, 1.68; 95% confidence interval, 0.94-3.01). CONCLUSIONS: Our data are preliminary but suggest that BRCA1 185delAG germline mutation is frequent in Israeli ovarian cancer patients, irrespective of family history, and may confer an early-onset phenotype of ovarian cancer

BRCA1 Protein↗
PubMed1996

Reduced CaMKII-positive neurones in the accumbens shell of an animal model of attention-deficit hyperactivity disorder.

THIS study aimed at investigating putative neural substrates of attention-deficit hyperactivity disorder in children using the spontaneously hypertensive rat (SHR) as animal model and the Ca2+/calmodulin-dependent protein kinase II (CaMKII) as a marker in the nucleus accumbens, an interface between limbic and motor systems. In prehypertensive male SHR and Wistar-Kyoto rats image analysis of CaMKII immunocytochemistry showed more positive elements in the shell than in the core, and in the former a lower level in SHR. The data indicate a reduced number of nucleus accumbens modules available for limbic-motor integration revealing putative substrates of the altered attentional and reinforcement mechanisms demonstrated in the SHR and in children with attention-deficit hyperactivity disorder.

Animals↗
PubMed1996

Morphological plasticity in dendritic spines of cultured hippocampal neurons.

Rat hippocampal neurons, grown in dissociated culture for about 18 days, were exposed for 6 h to three days to stimuli which cause either an increase (GABAA antagonists, bicuculline or picrotoxin), or decrease (tetrodotoxin) in spontaneous neuronal activity. Individual neurons were stained with 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate and visualized with a confocal laser scanning microscope. GABA antagonists caused a marked, up to 60%, increase in spine density on secondary dendrites of cultured hippocampal neurons. This was associated with a small decrease in spine length. The rise in spine density was partially prevented by treatment with the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetra-acetate, or by blockade of protein synthesis with cycloheximide. Tetrodotoxin caused a marked elongation of dendritic spines (but did not cause a decrease in spine density comparable to the increase caused by picrotoxin). This effect was seen primarily but not exclusively in spines with no distinct head. Both treatments were most effective within 24 h of exposure. There were no other systematic effects of the drugs on the morphology of the dendritic spines. These results indicate that dendritic spines in cultured neurons depend on ongoing synaptic activity to maintain their shape, and that neurons respond to an increase in synaptic demand by an increase in spine density. Thus, dendritic spines are likely to have a role in short-term synaptic interaction rather than to constitute a long-term memory storage device.

Action Potentials↗
PubMed1996

Inhibition of experimentally induced cirrhosis in rats by hypothyroidism.

The coexistence of hyperkinetic circulation, hypermetabolism, and hyperactivity of the sympathetic nervous system is encountered in both cirrhosis and hyperthyroidism. Several drugs, such as propylthiouracil and propranolol, that are beneficial for treating some patients with chronic liver diseases are also prescribed for the treatment of thyrotoxicosis. We investigated the effects of experimentally induced hypo- and hyperthyroidism on the development of cirrhosis induced in rats by thioacetamide (TAA). We specifically examined whether hypothyroidism could prevent and hyperthyroidism could aggravate liver damage. Hypothyroidism induced by methimazole (MMI, 0.04%), propylthiouracil (PTU 0.05%), and by thyroidectomy was confirmed by a significant elevation of thyroid-stimulating hormone (TSH) levels. Hyperthyroidism (decreased TSH levels) was induced by eltroxin (ELT:50 micrograms/kg). Thirteen groups of 10 rats each were studied: euthyroid controls (3 groups: water, TAA 1.5 months, and TAA 3 months), hypothyroid (6 groups: MMI, PTU, surgical, MMI-TAA, PTU-TAA, surgical-TAA), and hyperthyroid (4 groups:ELT 1.5 months and 3 months, and ELT-TAA for 1.5 months and 3 months). Hepatic fibrosis (scored from 0 to 3) was significantly reduced (P < .0001) in hypothyroid rats as compared with euthyroid controls, and was aggravated in TAA-treated hyperthyroid rats (P < .0001). Quantitative microscopic analysis of liver biopsy specimens from all groups confirmed the semiquantitative histopathological scores (P < .001). Direct intrasplenic pressure measurement revealed a significant portal pressure elevation in the TAA and the ELT-treated rats (from 4.7 +/- 0.1 in the euthyroid group to 8.1 +/- 2.3 and 10.2 +/- 2.1 and 12.5 +/- 1.6 in the TAA, ELT and ELT-TAA groups, respectively). However, in the hypothyroid-TAA groups, the portal pressure was found to be within the euthyroid normal range (4.6 +/- 1.2 and 5.8 +/- 0.6 in the PTU-TAA and surgical-TAA, respectively). After 12 weeks, the mean spleen weight of rats receiving only TAA was significantly higher than the TAA-treated hypothyroid rats (P < .0001), indicating that the hypothyroid TAA-treated rats were less portal hypertensive. These results suggest that induced hypothyroidism can inhibit, whereas hyperthyroidism can aggravate, the development of cirrhosis in a rat model.

Animals↗
PubMed1995

Immediate early genes and brain DNA remodeling in the Naples high- and low-excitability rat lines following exposure to a spatial novelty.

The aim of these studies was to map the neural consequences of exposure to a spatial novelty on the expression of immediate gene (IEG) and on unscheduled brain DNA synthesis (UBDS) in two genetic models of altered activity and hippocampal functions, i.e., the Naples High- (NHE) and Low-excitability (NLE) rats. Adult male rats of NLE and NHE lines, and of a random-bred stock (NRB) were tested in a Làt-maze, and corner crossings, rearings, and fecal boli were counted during two 10-min tests 24 h apart. For IEG expression, rats were exposed to a Làt-maze with nonexposed or repeatedly exposed rats used as controls, and were sacrificed at different time intervals thereafter. For UBDS, rats were sacrificed immediately after the first or the second exposure o a Làt-maze. IEG expression was measured by immunocytochemistry for the FOS and JUN proteins. NRB rats exposed for the first time to the maze showed extensive FOS and JUN positive cells in the reticular formation, the granular and pyramidal neurons of hippocampus, the amygdaloid nuclei, all layers of somatosensory cortex, and the granule cells of the cerebellar cortex. The positivity, stronger in rats exposed for the first time, was present between 2 and 6 h and was prevented by the NMDA receptor antagonist CPP (5 mg/kg). The positivity was very low in NHE rats, and it was stronger in NLE compared to NRB rats. UBDS was measured in ex vivo homogenates of brain areas by the incorporation into DNA of 3H-[methyl]-thymidine given intraventricularly 15 min before test trial 1 or 2 (pulse of 0.5 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1995

Fetal echocardiography in detecting anomalous pulmonary venous connection: four false positive cases.

Prenatal detection of congenital heart disease is possible from the 16th week of pregnancy, the ideal time being the mid-trimester, when most cardiac abnormalities can be detected. However, identification of anomalous pulmonary venous connection is difficult before birth and the sensitivity of fetal echocardiography in detecting this anomaly is low. Four cases are reported in which fetal echocardiographic findings obtained during the third trimester of pregnancy were highly suggestive of anomalous pulmonary venous connection. Right ventricular and atrial dominance associated with an enlarged coronary sinus or dilated superior vena cava were identified and considered to be indirect markers of the anomaly. No other cardiac anomaly was detectable. In all cases right ventricular and atrial dominance with dilated coronary sinus or superior vena cava were confirmed after birth despite the presence of normal pulmonary venous connections. These results confirm that the prenatal detection of this condition is difficult and should be based on the direct visualisation of anomalous pulmonary venous connections. The sole detection of indirect signs, such as right atrial and ventricular dominance with or without a dilated coronary sinus, superior vena cava, or inferior vena cava, does not warrant the diagnosis of anomalous pulmonary venous connection. Since the pulmonary venous flow in the human fetus is not as small as is commonly assumed, an anomalous drainage should be detectable when present and therefore should be specifically sought if the anomaly is suspected. The reasons for the presence of such transient cardiac anomalies remain obscure, but they might be related to functional or morphological rearrangement of the heart during fetal and perinatal life.

Echocardiography↗
PubMed1995

In vivo functional analysis of the mouse estrogen receptor gene promoter: a transgenic mouse model to study tissue-specific and developmental regulation of estrogen receptor gene transcription.

Understanding the molecular and morphological basis of estrogen responsiveness in the various tissues and organs that make up an adult organism and its onset during ontogenesis requires identification of the genetic controls that determine timed expression of the estrogen receptor (ER) gene in multiple cell types. With this goal in mind, we describe here the results of the functional analysis of the mouse (m) ER gene promoter, carried out in vivo in transgenic mice. The mER gene promoter was cloned and spliced to the coding sequence of the bacterial lacZ gene (fused to the nuclear localization signal of SV40 large T: nls-beta-GAL) and then stably reintegrated into the genome of mice. Analysis of beta-GAL mRNA and protein expression in multiple organs of both female and male transgenic animals was then performed. Results show that the transgenic mER promoter, much like the endogenous one, is active in several organs and tissues of adult female and male mice. The first 0.4 kilobases of 5'-flanking DNA (up to -364) are sufficient to direct widespread expression of the transgene in mouse organs. This indicates that genetic elements functional in various cell types are included in this segment. Furthermore, the first exon and intron of the mER gene are necessary to achieve sexually dimorphic expression of the transgene in neurons located at specific sites within the central nervous system. These mER promoter transgenic mice will be useful in mapping estrogen- responsive cell types under different physiological and pathological conditions in vivo, in defining ontogenesis of estrogen action in the mouse, and in studying the mechanisms that regulate ER gene transcription.

Animals↗
PubMed1995

Morphological analysis of dendritic spine development in primary cultures of hippocampal neurons.

We monitored developmental alterations in the morphology of dendritic spines in primary cultures of hippocampal neurons using confocal laser scanning microscopy (CLSM) and the fluorescent marker Dil. Dissociated rat hippocampal neurons were plated on polylysine-coated glass cover slips and grown in culture for 1-4 weeks. Fixed cultures were stained with Dil and visualized with the CLSM. Spine density, spine length, and diameters of spine heads and necks were measured. Some cultures were immunostained for synaptophysin and others prepared for EM analysis. In the 1-3 week cultures, 92-95% of the neurons contained spiny dendrites. Two subpopulations of spine morphologies were distinguished. At 1 week in culture, "headless" spines constituted 50% of the spine population and were equal in length to the spines with heads. At 2, 3, and 4 weeks in culture headless spines constituted a progressively smaller fraction of the population and were, on average, shorter than spines with heads. Spines with heads had narrower necks than headless spines. At 3 weeks in culture, spines were associated with synaptophysin-immunoreactive labeling, resembling synaptic terminals. At 4 weeks in culture, only 70% of the Dil-filled cells had spiny dendrites, and the density of spines decreased. Ultrastructurally, the majority of dendritic spine-like structures at 1 week resembled long filopodia without synaptic contacts. The majority of axospinous synapses were on short "stubby" spines. At 3 weeks in culture, the spines were characteristic of those seen in vivo. They contained no microtubules or polyribosomes, were filled with a characteristic, filamentous material, and formed asymmetric synapses. These studies provide the basis for further analysis of the rules governing the formation, development, and plasticity of dendritic spines under controlled, in vitro conditions.

Animals↗
PubMed1994

Nitric oxide and long-term habituation to novelty in the rat.

The role of nitric oxide in learning and memory processes has been tested in the albino rat by a histochemical and a behavioral study, following behavioral habituation to spatial novelty. Histochemically, the neural consequences of behavioral testing were mapped in the brain by staining for NADPH-d, known to be a NOS, whereas behaviorally the formation of LTH has been interfered with by posttrial NOS-inhibition. In the histochemical study, adult male Sprague-Dawley rats were tested in a Làt-maze and sacrificed at different time intervals thereafter. Handled unexposed rats served as controls. The brains were perfused with aldheide and processed for NADPH-d staining. In unexposed control rats the basal expression of NADPH-d was low and scattered. It pertained to few cells in the neostriatum, cerebral cortex, and CA1 hippocampal regions. In contrast, rats that had been exposed for the first time to the maze (spatial novelty) showed NADPH-d activity in the dorsal hippocampus (granule cells, few hilar neurons, and some CA1 pyramidal cells), the caudate-putamen complex, the cerebellum, and in all layers of somatosensory cortex. The positivity was not due to activity per se, since immediately after exposure it was not different from baseline. In contrast, it was present by 2 h and decreased significantly 24 h later. In addition, a strong neuronal discharge induced by the convulsant pentylentetrazol did not induce NADPH-d 2 h afterwards. The staining was prevented by pretreatment with the NMDA receptor antagonist CPP (5 mg/kg) or with the NOS inhibitor L-NOARG (10 mg/kg). In the behavioral study, rats were given an intraperitoneal injection of 1-10 mg/kg (L-NOARG) or vehicle immediately following exposure to a Làt-maze. The highest dose used (10 mg/kg) disrupted habituation of the vertical component only, known to be mainly of emotional meaning. Conversely, both doses disrupted emotional habituation based on defecation scores. The data indicate that the formation of LTH to novelty triggers a cascade of neurochemical events also involving NOS neurons. Further, the widespread induction of NADPH-d by exposure to novelty suggests that spatial and emotional information processing activate neural networks across different organizational levels of the CNS.

Amino Acid Oxidoreductases↗
PubMed1993

Distributed changes in c-Fos and c-Jun immunoreactivity in the rat brain associated with arousal and habituation to novelty.

The effects of exposure to spatial novelty on expression of the immediate early gene (IEG) products c-Fos and c-Jun were mapped in the rat brain by immunohistochemistry. Adult male Sprague-Dawley rats were tested for 10 min in a Làt-maze, and corner-crossings, rearings, and fecal boli were recorded. Rats were sacrificed at different time intervals after exposure to the maze (0.5, 2, 6, or 24 h). Unexposed rats or rats repeatedly exposed for 3 days at 24 h interval served as controls. Nonperfused brains were processed for immunocytochemistry for c-Fos and c-Jun on adjacent slices using the avidin-biotin method and diaminobenzidine as chromogen. In unexposed control rats the constitutive expression of the two IEGs products was low and scattered. In contrast, rats that had been exposed for the first time to the maze (spatial novelty) showed an extensive c-Fos- and c-Jun-like immunoreactivity in the reticular formation, the caudate-putamen complex, the hippocampus (granular and pyramidal neurons), the cerebellum (granular neurons), and all layers of somatosensory cortex. The positivity was stronger in rats exposed for the first time to the box than in repeatedly exposed or unexposed control rats. A maximal IEG expression was found in animals with postexposure survival times of 2 and 6 h. IEG expression in repeatedly exposed rats was still above baseline expression of unexposed rats but still lower than that of rats having been exposed only once to the maze.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Spontaneous closure of inlet ventricular septal defect in an infant with Down's syndrome and aortic coarctation.

Ventricular septal defect (VSD) is considered one of the most common congenital heart diseases in patients with Down's syndrome. It is well known that some VSDs show a tendency to diminish in size and to close. To our knowledge, in patients with Down's syndrome spontaneous closure of a perimembranous inlet VSD has not been described before. The prevalence of some cardiac malformations and the rarity of others have been reported in patients with Down's syndrome. Left ventricular outflow tract obstruction rarely occurs in patients with Down's syndrome. A case of Down's syndrome with coarctation of the aorta, patent ductus arteriosus, and perimembranous inlet VSD that spontaneously closed by formation of aneurysm of the membranous septum is reported.

Abnormalities, Multiple↗
PubMed1993

Radioimmunodetection of colorectal cancer metastases with 131I-labeled monoclonal antibody B72.3: a pilot study to determine efficacy of detection and pharmacokinetics.

We performed radioimmunoscintigraphy (RIS) and/or pharmacokinetic (PCK) studies in 12 patients with primary or metastatic colorectal carcinoma, utilizing an intravenous administration of 1-4 mCi (1 mg) of 131I-B72.3 monoclonal antibody. Metastatic lesions were correctly identified in 4/8 patients by RIS. Two patients with small lesions (> 2 cm diameter) had a false-negative RIS scan. Two patients had a true-negative RIS scan. Optimal images were obtained at 1 week postinjection. PCK studies showed that the plasma clearance of 131I-B72.3 was biexponential with an alpha-phase half-life ranging from 0.5 to 7.1 hr and a beta-phase half-life ranging from 47.5 to 85.3 hr. Systemic and renal clearance data indicated that 131I-B72.3 was cleared very slowly and almost entirely by deiodination. This pilot study was conducted to gain an understanding of the pharmacokinetics of this radiolabeled antibody. On the basis of these data, we are now studying second-generation antibodies as part of our long-range objectives to incorporate them in early detection and treatment protocols.

Adult↗
PubMed1992

Autoimmune mechanisms in thromboangiitis obliterans (Buerger's disease): the role of tobacco antigen and the major histocompatibility complex.

This study is a continuation of our previous work that showed that patients with thromboangiitis obliterans (TAO; Buerger's disease) demonstrate a cell-mediated immune response to human artery type-specific collagens. To investigate the role of cigarette smoking in patients with TAO, cellular and humoral sensitivity was tested to a tobacco glycoprotein (TGP) antigen in 13 patients with Buerger's disease, 16 healthy smokers, and 12 nonsmoking healthy young male subjects. In this study, patients with Buerger's disease and healthy smokers had the same rate of cellular response to TGP, whereas nonsmokers did not respond. All three groups had a 30% to 40% measurable antibody response to TGP. If TGP has an immunologic role in the pathogenesis of TAO, an additional factor (or factors) may be operative. A specific genetic makeup may be one such factor, although at this stage other pathogenic mechanisms cannot be ruled out. Eleven patients with Buerger's disease and two control groups of 10 young healthy smoking male subjects and 12 young nonsmokers underwent histocompatibility leukocyte antigen (HLA) typing. Patients with Buerger's disease had a statistically significantly higher frequency of HLA-DR4 and a significantly lower frequency of the HLA-DRW6 antigen than had both control groups. Because similar findings have been reported in other autoimmune diseases, this observation may serve as further evidence that an autoimmune mechanism is involved in Buerger's disease.

Antibody Formation↗